Category Archives: Transhuman News

PHILADELPHIA A new form ofgene therapyfor boys with X-linked severe combined immunodeficiency syndrome (SCID-X1), a life-threatening condition also known as bubble boy disease, appears to be both effective and safe, according to an international clinical trial with sites inBoston, Cincinnati, Los Angeles, London, and Paris.

Early data published in theNew England Journal of Medicinesuggests that the therapy may avoid the late-developing leukemiaseen in a quarter of SCID-X1 patients in previous gene-therapy trials in Europe that took place more than a decade ago. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.

The lab of coauthorFrederic Bushman, PhD, professor of Microbiology, from thePerelman School of Medicine at the University of Pennsylvania, carried out the deep DNA sequencing on patient specimens to track and verify distributions of integration sites of the vector.The vector used in the new trial was engineered to remove molecular signals implicated in cancers in the first trial.

Eight of nine boys recruited to date to the present trial are alive between 12 and 38 months after treatment, with no SCID-X1-associated infections. The gene therapy alone generated functioning immune systems in seven of eight boys. Genetic studies showed that the new viral vector did not lead to vector insertions near known cancer-causing genes, raising cautious hopes about the vector's long-term safety.

We showed that fewer cells accumulated with integration sites near cancer genes in the second trial, suggesting that the adverse properties had indeed been engineered out, explains Bushman So far there are no clinical adverse events in the present trial -- the integration site data has suggested improved safety.

The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on oncogenes that could lead to leukemia.

The core question of the trial was whether the new self-inactivating viral vector could safely and successfully shuttle a gene called theIL-2 receptor gamma(IL2RG) subunit into the patients' hematopoietic stem cells. In boys born with SCID-X1, mutations render theIL2RGgene inactive, robbing the children of the ability to produce a functional immune system.

For more information, see theDana-Farber/Boston Children's Cancer and Blood Disorders Centersnews release.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania(founded in 1765 as the nation's first medical school) and theUniversity of Pennsylvania Health System, which together form a $4.3 billion enterprise.

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New Gene Therapy for "Bubble Boy" Disease Appears to be Safe, Effective

PUBLIC RELEASE DATE:

14-Oct-2014

Contact: Matt Solovey msolovey@hmc.psu.edu 717-531-8606 Penn State @penn_state

Slow-healing or non-healing bone fractures in otherwise healthy people may be caused by gene variants that are common in the population, according to Penn State College of Medicine researchers.

"We found associations between certain gene polymorphisms and delayed fracture healing in a sample of patients," said J. Spence Reid, professor of orthopaedics and rehabilitation. "Our study was preliminary but it demonstrated the feasibility of a larger one, which we're now working to set up."

The identification of gene variants that delay fracture healing could lead to screening tests for patients with broken bones. Those patients deemed likely to experience slow healing could be given more aggressive treatment when they first reach the hospital, potentially avoiding months of debilitation.

The researchers reported their results in the Journal of Bone and Joint Surgery.

Of the eight million bone fractures in the U.S. every year, about 10 percent fail to heal normally. Smoking, diabetes, NSAID use, low vitamin D levels and old age are known risk factors, but in a significant subset of cases, unknown factors appear to be involved.

"Some fractures are slow-healing for no obvious reason, and we wondered if there is a genetic basis for those cases," said Reid.

He and his colleagues selected from their records 33 patients diagnosed with "atrophic nonunion" -- the failure of a fracture to knit together on its own within six months. As controls, they selected 29 patients whose fractures had healed normally.

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Common gene variants linked to delayed healing of bone fractures

PUBLIC RELEASE DATE:

15-Oct-2014

Contact: Rhiannon Bugno Biol.Psych@utsouthwestern.edu 214-648-0880 Elsevier @ElsevierConnect

Philadelphia, PA, October 15, 2014 Are deficits in attention limited to those with attention-deficit/hyperactivity disorder (ADHD) or is there a spectrum of attention function in the general population? The answer to this question has implications for psychiatric diagnoses and perhaps for society, broadly.

A new study published in the current issue of Biological Psychiatry, by researchers at Cardiff University School of Medicine and the University of Bristol, suggests that there is a spectrum of attention, hyperactivity/impulsiveness and language function in society, with varying degrees of these impairments associated with clusters of genes linked with the risk for ADHD.

Viewing these functions as dimensions or spectrums contrasts with a traditional view of ADHD as a disease category.

To answer this question, researchers led by senior author Dr. Anita Thapar used genetic data from patients with ADHD as well as data from the Avon Longitudinal Study of Parents and Children (ALSPAC). The ALSPAC is based in England and is a large, ongoing study of parents and children followed since birth in the early '90s.

They created polygenic risk scores a 'composite' score of genetic effects that forms an index of genetic risk of ADHD for 8,229 ALSPAC participants.

They found that polygenic risk for ADHD was positively associated with higher levels of traits of hyperactivity/impulsiveness and attention at ages 7 and 10 in the general population. It was also negatively associated with pragmatic language abilities, e.g., the ability to appropriately use language in social settings.

"Our research finds that a set of genetic risks identified from UK patients with a clinical diagnosis of childhood ADHD also predicted higher levels of developmental difficulties in children from a UK population cohort, the ALSPAC," said Thapar.

Original post:
Gene variants implicated ADHD identify attention and language deficits general population